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Journal of Advanced Pharmaceutical... 2024Luteolin exhibited antibacterial activity against and its chemical structure similar to that of ciprofloxacin (CPF) which works by inhibiting DNA gyrase. Filtrate from...
Luteolin exhibited antibacterial activity against and its chemical structure similar to that of ciprofloxacin (CPF) which works by inhibiting DNA gyrase. Filtrate from passion fruit extract containing luteolin and its derivatives could inhibit extended-spectrum β-lactamase (ESBL)-producing . . Antibacterial compounds that can also inhibit ESBL will be valuable compounds to overcome the problem of resistant bacteria. This study aimed to ensure the potency of luteolin and luteolin derivatives targeting DNA gyrase and ESBL by approach. Docking simulation of ligands L1-L14 was performed using AutoDock Vina, and pharmacokinetics and toxicity (absorption, distribution, metabolism, excretion, and toxicity) profiles were predicted by pKCSM online. The docking result revealed higher binding affinity on DNA gyrase (PDB.1KZN) of 12 luteolin derivatives (energy <-7.6 kcal/mol) compared to CPF and higher affinity (energy <-6.27 kcal/mol) of all compounds than clavulanic acid against ESBL CTX-M-15 (PDB.4HBU). The compounds could be absorbed through the human intestine moderately, which showed low permeability to blood-brain barrier, nontoxic and nonhepatotoxic. The most active luteolin glycoside (L6) is capable to inhibit DNA gyrase and ESBL from which provided the potential against resistant bacteria and was promoted as lead compounds to be developed further.
PubMed: 38389968
DOI: 10.4103/JAPTR.JAPTR_217_23 -
Scientific Reports Feb 2024The spread of fluoroquinolone (FQ) resistance in Acinetobacter baumannii represents a critical health threat. This study aims to overcome FQ resistance in A. baumannii...
The spread of fluoroquinolone (FQ) resistance in Acinetobacter baumannii represents a critical health threat. This study aims to overcome FQ resistance in A. baumannii via the formulation of polymeric nanoFQs. Herein, 80 A. baumannii isolates were obtained from diverse clinical sources. All A. baumannii isolates showed high resistance to most of the investigated antimicrobials, including ciprofloxacin (CIP) and levofloxacin (LEV) (97.5%). FQ resistance-determining regions of the gyrA and parC genes were the most predominant resistant mechanism, harbored by 69 (86.3%) and 75 (93.8%) of the isolates, respectively. Additionally, plasmid-mediated quinolone resistance genes aac(6')-Ib and qnrS were detected in 61 (76.3%) and 2 (2.5%) of the 80 isolates, respectively. The CIP- and LEV-loaded poly ε-caprolactone (PCL) nanoparticles, F and F, respectively, showed a 1.5-6- and 6-12-fold decrease in the MIC, respectively, against the tested isolates. Interestingly, the time kill assay demonstrated that MICs of F and F completely killed A. baumannii isolates after 5-6 h of treatment. Furthermore, F and F were found to be efficient in overcoming the FQ resistance mediated by the efflux pumps in A. baumannii isolates as revealed by decreasing the MIC four-fold lower than that of free CIP and LEV, respectively. Moreover, F and F at 1/2 and 1/4 MIC significantly decreased biofilm formation by 47-93% and 69-91%, respectively. These findings suggest that polymeric nanoparticles can restore the effectiveness of FQs and represent a paradigm shift in the fight against A. baumannii isolates.
Topics: Ciprofloxacin; Fluoroquinolones; Levofloxacin; Acinetobacter baumannii; Anti-Bacterial Agents; Microbial Sensitivity Tests; Biofilms; Drug Resistance, Bacterial; DNA Gyrase
PubMed: 38326515
DOI: 10.1038/s41598-024-53441-1 -
Saudi Pharmaceutical Journal : SPJ :... Mar 2024Tetrazole-based derivatives and their electronic structures have displayed interesting antimicrobial activity.
BACKGROUND
Tetrazole-based derivatives and their electronic structures have displayed interesting antimicrobial activity.
METHODS
The tetrazole-based hybrids linked with thiazole, thiophene and thiadiazole ring systems have been synthesized through various chemical reactions. The computational method DFT/B3LYP has been utilized to calculate their electronic properties. The antimicrobial effectiveness was investigated against representative bacterial and fungal strains. Additionally, the synthesized derivatives binding interaction was stimulated by docking program against PDB ID: 4URO as a model of the ATP binding domain of DNA Gyrase subunit B.
RESULTS
The structures of the synthesized tetrazole-based derivatives were confirmed by IR, NMR, and Mass spectroscopic data. The DFT/B3LYP method showed that the thiadiazole derivatives had lower ΔE than the thiophenes and thiazoles . The hybrids , , and exhibited proper antibacterial activity against Gram's +ve bacterial strains ( and ), while displayed potent activity towards Gram's -ve bacterial strains ( and ). Meanwhile, derivatives , , , and showed good effectiveness towards fungal strain ().
CONCLUSION
The study provides valuable tetrazole core-linked heterocyclic rings and opens the door to further research on their electrical characteristics and applications. Tetrazoles and thiazoles have antibacterial properties in pharmacological frameworks, making these hybrids potential lead molecules for drug development. The conclusion summarizes the data and suggests that the synthesized chemicals' interaction with a particular protein domain suggests focused biological activity.
PubMed: 38318318
DOI: 10.1016/j.jsps.2024.101962 -
MBio Feb 2024is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen...
is an obligate intracellular bacterium that is responsible for the most prevalent bacterial sexually transmitted infection. Changes in DNA topology in this pathogen have been linked to its pathogenicity-associated developmental cycle. Here, evidence is provided that the balanced activity of DNA topoisomerases contributes to controlling developmental processes. Utilizing catalytically inactivated Cas12 (dCas12)-based clustered regularly interspaced short palindromic repeats interference (CRISPRi) technology, we demonstrate targeted knockdown of chromosomal transcription in without detected toxicity of dCas12. Repression of impaired the developmental cycle of mostly through disruption of its differentiation from a replicative form to an infectious form. Consistent with this, expression of late developmental genes of was downregulated, while early genes maintained their expression. Importantly, the developmental defect associated with knockdown was rescued by overexpressing at an appropriate degree and time, directly linking the growth patterns to the levels of expression. Interestingly, knockdown had effects on DNA gyrase expression, indicating a potential compensatory mechanism for survival to offset TopA deficiency. with knocked down displayed hypersensitivity to moxifloxacin that targets DNA gyrase in comparison with the wild type. These data underscore the requirement of integrated topoisomerase actions to support the essential developmental and transcriptional processes of .IMPORTANCEWe used genetic and chemical tools to demonstrate the relationship of topoisomerase activities and their obligatory role for the chlamydial developmental cycle. Successfully targeting the essential gene with a CRISPRi approach, using dCas12, in indicates that this method will facilitate the characterization of the essential genome. These findings have an important impact on our understanding of the mechanisms by which well-balanced topoisomerase functions in adaptation of to unfavorable growth conditions imposed by antibiotics.
Topics: Chlamydia trachomatis; DNA Gyrase; DNA Topoisomerases, Type I; Bacterial Proteins
PubMed: 38265209
DOI: 10.1128/mbio.02584-23 -
Frontiers in Microbiology 2023Myxobacteria have a complex life cycle and unique social behavior, and obtain nutrients by preying on bacteria and fungi in soil. Chitinase, β-1,3 glucanase and β-1,6... (Review)
Review
Myxobacteria have a complex life cycle and unique social behavior, and obtain nutrients by preying on bacteria and fungi in soil. Chitinase, β-1,3 glucanase and β-1,6 glucanase produced by myxobacteria can degrade the glycosidic bond of cell wall of some plant pathogenic fungi, resulting in a perforated structure in the cell wall. In addition, isooctanol produced by myxobacteria can lead to the accumulation of intracellular reactive oxygen species in some pathogenic fungi and induce cell apoptosis. Myxobacteria can also perforate the cell wall of some plant pathogenic oomycetes by β-1,3 glucanase, reduce the content of intracellular soluble protein and protective enzyme activity, affect the permeability of oomycete cell membrane, and aggravate the oxidative damage of pathogen cells. Small molecule compounds such as diisobutyl phthalate and myxovirescin produced by myxobacteria can inhibit the formation of biofilm and lipoprotein of bacteria, and cystobactamids can inhibit the activity of DNA gyrase, thus changing the permeability of bacterial cell membrane. Myxobacteria, as a new natural compound resource bank, can control plant pathogenic fungi, oomycetes and bacteria by producing carbohydrate active enzymes and small molecular compounds, so it has great potential in plant disease control.
PubMed: 38260911
DOI: 10.3389/fmicb.2023.1294854 -
RSC Advances Jan 2024Benzothiazole-based bacterial DNA gyrase and topoisomerase IV inhibitors are promising new antibacterial agents with potent activity against Gram-positive and...
Benzothiazole-based bacterial DNA gyrase and topoisomerase IV inhibitors are promising new antibacterial agents with potent activity against Gram-positive and Gram-negative bacterial strains. The aim of this study was to improve the uptake of these inhibitors into the cytoplasm of Gram-negative bacteria by conjugating them to the small siderophore mimics. The best conjugate 18b displayed potent DNA gyrase and topoisomerase IV inhibition. The interaction analysis of molecular dynamics simulation trajectory showed the important contribution of the siderophore mimic moiety to binding affinity. By NMR spectroscopy, we demonstrated that the hydroxypyridinone moiety alone was responsible for the chelation of iron(iii). Moreover, 18b showed an enhancement of antibacterial activity against JW5503 in an iron-depleted medium, clearly indicating an increased uptake of 18b in this bacterial strain.
PubMed: 38239435
DOI: 10.1039/d3ra08337c -
Evidence-based Complementary and... 2024Cow urine distillate (CUD) is a traditional Indian medicine used to treat various diseases, including bacterial infections. However, there is limited evidence to support...
Cow urine distillate (CUD) is a traditional Indian medicine used to treat various diseases, including bacterial infections. However, there is limited evidence to support its use as a medicine, and its safety and efficacy have not been thoroughly studied. In this study, we evaluated the antibacterial activity of CUD against five bacterial strains using in vitro and in silico approaches. In vitro experiments showed that CUD has significant antibacterial activity against all tested strains with a zone of inhibition (ZOI) ranging from 13 to 24 mm and minimum inhibitory concentration (MIC) values ranging from 12.5 to 50 g/ml. The results indicated that the 15% concentration of CUD displayed the highest antibacterial activity against and . To further investigate the antibacterial mechanism of CUD, we performed in silico docking studies of the active compounds of CUD with bacterial proteins involved in protein synthesis. Our results showed that 2-hydroxycinnamic acid (Δ = -6.9 kcal/mol) and ferulic acid (Δ = -6.8 kcal/mol) exhibited the best docking scores with the targeted proteins (DNA gyrase, PDBID: 4KFG). The hydrogen bonding interaction with amino acids Val71 and Asp73 was found to be crucial for their antibacterial activity.
PubMed: 38225974
DOI: 10.1155/2024/1904763 -
ACS Omega Jan 2024A coprecipitation approach was employed to synthesize aluminum oxide (AlO) with a fixed quantity of graphitic carbon nitride (g-CN) and various concentrations of Mg (2...
A coprecipitation approach was employed to synthesize aluminum oxide (AlO) with a fixed quantity of graphitic carbon nitride (g-CN) and various concentrations of Mg (2 and 4 wt. %). The main objective of this research is to explore and enhance the dye degradation potential and antimicrobial efficacy of synthesized pristine and doped AlO with molecular docking analysis. AlO has potent mechanical, thermal, antimicrobial, phosphoric, optical, and electrical properties, but it leaches into water and has a high band gap and low refractive index. g-CN was incorporated into AlO to increase the degradation potency. The incorporation of Mg enhances the metal oxide characteristics and performance in catalysis. XRD patterns revealed the orthorhombic phase of AlO. The SAED pattern of AlO and (2 and 4 wt %) Mg/g-CN-AlO nanostructures (NSs) showed bright polycrystalline rings. UV-visible spectra showed the absorption of AlO at 289 nm, and upon doping, a blue shift was accompanied. The EDS spectra indicated the existence of Al, O, Na, and Mg, thereby verifying the elemental composition of the pristine and doped samples. TEM images revealed the nanowires (NWs) of AlO. The NSs demonstrated outstanding catalytic performance for the remediation of RhB dye in a basic medium of around 97.36%. Mg/g-CN-AlO (4 wt %) exhibited a notable augmentation in the inhibition zone, measuring 5.25 mm, when exposed to high-level doses against . In silico predictions have recently shed light on the underlying mystery of the bactericidal actions of these doped NSs against specific enzyme targets such as DNA gyrase.
PubMed: 38222666
DOI: 10.1021/acsomega.3c08077 -
ACS Omega Jan 2024(Cucurbitaceae) is a plant traditionally used against diarrhea, teeth-ach, wounds, stomach ache, meningitis, and cancer. The extracts of after silica gel column...
(Cucurbitaceae) is a plant traditionally used against diarrhea, teeth-ach, wounds, stomach ache, meningitis, and cancer. The extracts of after silica gel column chromatography gave nine compounds identified using spectroscopic methods such as hexacosane (), octadecane (), 17-(-5-ethyl-2,6-dihydroxy-6-methylhept-3-en-2-yl)-9-(hydroxymethyl)-13-methylcyclopenta[α]phenanthren-3-ol (), erythrodiol (), (9,12)-propyl icosa-9,12-dienoate (), α-spinasterol (), 16-dehydroxycucurbitacin (), cucurbitacin D (), and 23,24-dihydroisocucurbitacin D (). Compounds and are new to the genus . α-Spinasterol showed better inhibition zone diameter = 13.67 ± 0.57, 15.00 ± 0.10, and 13.33 ± 0.57 mm against , and compared with the other tested samples. α-Spinasterol (-8.0 kcal/mol) and (-7.6 kcal/mol) displayed high binding affinity against DNA Gyrase compared to ciprofloxacin (-7.3 kcal/mol). α-Spinasterol and 16-dehydroxycucurbitacin showed better binding affinity against protein kinase. The cytotoxicity results revealed that the EtOAc extract showed the highest potency with IC = 16.05 μg/mL. 16-Dehydroxycucurbitacin showed a higher binding affinity (-7.7 kcal/mol) against human topoisomerase IIβ than etoposide. The cytotoxicity and antibacterial activities and in silico molecular docking analysis displayed by the constituents corroborate the traditional use of the plant against bacteria and cancer.
PubMed: 38222496
DOI: 10.1021/acsomega.3c08866 -
ACS Omega Dec 2023Peptide synthesis has opened new frontiers in the quest for bioactive molecules with limitless biological applications. This study presents the synthesis of a series of...
Synthesis and Evaluation of Biological Activities for a Novel 1,2,3,4-Tetrahydroisoquinoline Conjugate with Dipeptide Derivatives: Insights from Molecular Docking and Molecular Dynamics Simulations.
Peptide synthesis has opened new frontiers in the quest for bioactive molecules with limitless biological applications. This study presents the synthesis of a series of novel isoquinoline dipeptides using advanced spectroscopic techniques for characterization. These compounds were designed with the goal of discovering unexplored biological activities that could contribute to the development of novel pharmaceuticals. We evaluated the biological activities of novel compounds including their antimicrobial, antibacterial, and antifungal properties. The results show promising activity against and potent antibacterial activity against MTCC 443 and MTCC 1688. Furthermore, these compounds demonstrate strong antifungal activity, outperforming existing standard drugs. Computational binding affinity studies of tetrahydroisoquinoline-conjugated dipeptides against DNA gyrase displayed significant binding interactions and binding affinity, which are reflected in antimicrobial activities of compounds. Our integrative significant molecular findings from both wet and dry laboratories would help pave a path for the development of antimicrobial therapeutics. The findings suggest that these isoquinoline-conjugated dipeptides could be excellent candidates for drug development, with potential applications in the fight against bacterial and fungal infections. This research represents an exciting step forward in the field of peptide synthesis and its potential to discover novel bioactive molecules with significant implications for human health.
PubMed: 38162790
DOI: 10.1021/acsomega.3c05961